Animal Models & Tissue Engineering Core

Co-directors:
Howard Levinson, MD
Associate Professor in Surgery
howard.levinson@duke.edu

Jennifer Zhang, PhD
Associate Professor in Dermatology
Assistant Professor in Pathology
jennifer.zhang@dm.duke.edu

Tissue models with a complex cell system and an intact circulation are critical aspects of basic and translational research. The goal of the Animal Models and Tissue Engineering Core (AMTEC) is to provide service for a broad range of skin tissue models to the Duke Research Community. The core encompasses three specific aims:

  1. To provide access to regenerated human skin tissues with defined genetic changes.

Human and mouse skin tissues display a number of architectural and developmental differences such as the thickness of the epidermis, the density of hair follicles and frequency in cycling. These differences necessitate the use of human skin tissues for biological and drug developmental studies, as well as imaging guided-diagnostic studies.

Three different formats of human tissues are available:

    • 3-D skin culture with normal or genetically modified keratinocytes, melanocytes and dermal cells,
    • De novo skin regeneration on immunodeficient mice with genetically edited keratinocytes, melanocytes and dermal cells,
    • Xenotransplant of normal or diseased human full-thickness skin onto immunodeficient mice.

2. To provide consultation and technical assistance in the use of various cutaneous wound healing and scarring models for mechanistic and drug developmental studies.

Chronic non healing skin wounds and hypertrophic scarring are major unmet medical needs. The AMTEC will provide consultations in animal model selection and research design, education and technical assistance in project execution, data analysis and interpretation.

    • A full-service of various murine and swine surgical animal models on the specific genetic backgrounds of your interest.
    • A wide spectrum of tools commonly used for outcome measures, including tissue mechanics, morphometry, biochemistry, wound size and appearance, epithelialization, granulation tissue formation, angiogenesis, and inflammation.
    • Delivery of agents and therapeutics such as drugs, nucleic acids, viruses, cells, antibodies, or proteins through intravenous, subcutaneous, topical, oral, intrathecal, intra-peritoneal, or osmotic pumps.

3. To provide consultation and access to various skin-focused genetic mouse models.

Mouse models of skin disease have been a powerful tool for identifying and modeling human skin disease. This core will provide the following services:

    • Transplantation of embryonic, newborn or adult mouse skin tissues onto nude of SCID mouse through surface grafting.
    • Advice and support for investigators wishing to use the two-stage chemical induced skin carcinogenesis protocol.
    • To provide advice, guidance and access to genetic mouse lines useful for skin research. These include Cre lines for tissue specific and inducible gene knockout in various epidermal and dermal cell types, lines for induced expression in epidermal cells, floxed and knockout alleles of genes important for skin biology and fluorescent-fusion proteins expressed in the epidermis. These animal models will be made available to members of SDCR.

Estimated Price:

1. Human Skin Regeneration:

We typically recommend 3-5 grafts/group.

    • 3-D culture: $50/graft
    • De novo human skin regeneration on NSG or NC17.SCID mice: $125/graft
    • Xenotransplant of normal or diseased skin on NSG or NC17.SCID mice: $75/graft

2. Wound healing and scarring models.

We typically recommend 8 wounds per group, based on a power analysis.

    • We estimate 4 groups per study (3 experimental groups and 1 control group), with 1 wound per animal. We would continuously analyze healing up to 30 days post-operatively. Tissue analyses would be offered only at one time point, on day 30.
    • Rodent study:
      • For a rodent study 32 rodents ~$640 in animal purchasing.
      • Housing costs are ~$1/cage/day for up to 5 rodents=$7/day. We estimate a 30 day study to be $210 in husbandry.
    • Swine study:
      • For a swine study, this would range from 1-4 swine, such as a Yucatan mini-pig. This would amount to ~$3200 in animal purchasing.
      • Housing costs are ~$17/cage/day for 1 swine=$68/day. If we estimate a 30 day study, this would be $2040 in husbandry.
    • Analyses include healing time, toxicity monitoring, and basic histology (H&E) and immunohistology (CD31 for angiogenesis, F4/80 for macrophages, and DAPI for cellularity).

3. Embryonic or newborn mouse skin grafting:

    • $50/graft